Jie Jane Chen1, Jeremy P Harris2, Christina S Kong3, John B Sunwoo4, Vasu Divi4, Kathleen C Horst2, Sumaira Z Aasi5, S Tyler Hollmig5, Wendy Y Hara6. 1. Harvard Medical School, Boston, MA, USA; Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA. 2. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA. 3. Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. 4. Department of Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA. 5. Department of Dermatology, Stanford University School of Medicine, Stanford, CA, USA. 6. Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: whara808@gmail.com.
Abstract
OBJECTIVES: Clinical perineural invasion (CPNI) of cutaneous head and neck cancer is associated with poor prognosis and presents a therapeutic dilemma. The purpose of this study was to determine the relationship between CPNI and nerve growth factor receptors (NGFR), and the impact of radiotherapy (RT), imaging, and NGFR on symptom control and disease-related outcomes. MATERIALS AND METHODS: We retrospectively reviewed patients with CPNI of cutaneous head and neck cancer who were treated with RT between 2010 and 2015 at our institution. Exact chi-square and Wilcoxon rank-sum tests compared patients with positive versus negative staining for TrkA and/or CD271. Gray's test determined differences in cumulative incidences of 1- and 2-year locoregional recurrence (LRR) and cancer-specific mortality (CSM). RESULTS: Twenty-three patients had a median overall follow-up of 31.4 months from initial clinical symptoms and 19.7 months from pathological confirmation of PNI. The most prevalent symptoms were numbness (70%) and pain (57%). Sixteen patients (70%) experienced symptom improvement or control, especially decreased pain (85%), within a median of 2.6 months from starting RT. The 1- and 2-year rates of overall LRR were 37% and 71%, while those of overall CSM were 11% and 25%, respectively. Patients who stained positively for TrkA and/or CD271 had significantly worse LRR compared to patients who stained negatively for both markers (p = 0.046). CONCLUSION: Positive TrkA and/or CD271 staining predicts worse outcomes. Patients may benefit from aggressive RT for local control and symptom improvement. Future research is needed to identify the potential for anti-nerve growth factor therapies in CPNI.
OBJECTIVES: Clinical perineural invasion (CPNI) of cutaneous head and neck cancer is associated with poor prognosis and presents a therapeutic dilemma. The purpose of this study was to determine the relationship between CPNI and nerve growth factor receptors (NGFR), and the impact of radiotherapy (RT), imaging, and NGFR on symptom control and disease-related outcomes. MATERIALS AND METHODS: We retrospectively reviewed patients with CPNI of cutaneous head and neck cancer who were treated with RT between 2010 and 2015 at our institution. Exact chi-square and Wilcoxon rank-sum tests compared patients with positive versus negative staining for TrkA and/or CD271. Gray's test determined differences in cumulative incidences of 1- and 2-year locoregional recurrence (LRR) and cancer-specific mortality (CSM). RESULTS: Twenty-three patients had a median overall follow-up of 31.4 months from initial clinical symptoms and 19.7 months from pathological confirmation of PNI. The most prevalent symptoms were numbness (70%) and pain (57%). Sixteen patients (70%) experienced symptom improvement or control, especially decreased pain (85%), within a median of 2.6 months from starting RT. The 1- and 2-year rates of overall LRR were 37% and 71%, while those of overall CSM were 11% and 25%, respectively. Patients who stained positively for TrkA and/or CD271 had significantly worse LRR compared to patients who stained negatively for both markers (p = 0.046). CONCLUSION: Positive TrkA and/or CD271 staining predicts worse outcomes. Patients may benefit from aggressive RT for local control and symptom improvement. Future research is needed to identify the potential for anti-nerve growth factor therapies in CPNI.